Characterization of gut microbiome signatures in metabolic dysfunction associated steatotic liver disease

This cross-sectional study compared the gut microbiota between metabolic dysfunction associated steatotic liver disease (MASLD) patients and healthy controls. A total of 1401 participants, including 392 MASLD patients and 1009 healthy controls, were enrolled from one project site of the Healthy Zhejiang One Million People Cohort (HOPE) between January 2022 and June 2023. Shotgun metagenomic sequencing was conducted to compare the composition and functional profiles of the gut microbiome between MASLD patients and healthy controls. Compared to the control group, MASLD patients exhibited significant alterations in both alpha and beta diversity, along with reduced connectivity and robustness of the gut microbial network. We identified significant changes in the abundance of 12 microbial strains between the two groups with two strains (t_SGB4749 and t_SGB4753) enriched and ten strains depleted in MASLD patients. In comparison to the control group, MASLD patients demonstrated distinct differences in the genomic potential related to increased glycolysis, decreased pyruvate metabolism, and elevated lipopolysaccharide (LPS) biosynthesis in both metagenomic functional profiling and single-strain genome analysis. These findings suggest that alterations in specific microbial strains and metabolic pathways may contribute to MASLD pathogenesis.